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Review
. 2021 Jun 17;1(1):ltab007.
doi: 10.1093/immadv/ltab007. eCollection 2021 Jan.

Adaptive immunity and vaccination - iron in the spotlight

Alexandra E Preston  1 , Hal Drakesmith  1   2 , Joe N Frost  1
Affiliations
Review

Adaptive immunity and vaccination - iron in the spotlight

Alexandra E Preston et al. Immunother Adv. .

Abstract

Vaccination programmes are critically important to suppress the burden of infectious diseases, saving countless lives globally, as emphasised by the current COVID-19 pandemic. Effective adaptive immune responses are complex processes subject to multiple influences. Recent genetic, pre-clinical, and clinical studies have converged to show that availability of iron is a key factor regulating the development of T and B cell responses to infection and immunisation. Lymphocytes obtain iron from circulating transferrin. The amount of iron bound to transferrin is dependent on dietary iron availability and is decreased during inflammation via upregulation of the iron-regulatory hormone, hepcidin. As iron deficiency and chronic inflammatory states are both globally prevalent health problems, the potential impact of low iron availability on immune responses is significant. We describe the evidence supporting the importance of iron in immunity, highlight important unknowns, and discuss how therapeutic interventions to modulate iron availability might be implementable in the context of vaccination and infectious disease.

Keywords: adaptive immunity; hepcidin; iron; vaccination.

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Figures

Figure 1.
Figure 1.
Inflammation, often resulting from infection, induces hepcidin expression via IL-6, driving hypoferraemia. Hypoferraemia poses a trade-off to the host, limiting extracellular iron availability and protecting against siderophilic pathogens (e.g. Vibrio vulnificus), but also diverting iron away from the adaptive immune response, impairing control of pathogenic viruses (e.g. Influenza A virus infection).
Figure 2.
Figure 2.
Dietary factors and constitutively high hepcidin expression can drive low serum iron availability. Sufficient iron concentrations are required to generate a robust adaptive immune response. In particular settings, it may be possible to acutely supplement serum iron availability to support immunity, thereby improving vaccine efficacy – this concept remains to be investigated.
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References

    1. Muchowska KB, Varma SJ, Moran J. Synthesis and breakdown of universal metabolic precursors promoted by iron. Nature 2019;569(7754):104–7. doi:10.1038/s41586-019-1151-1 - DOI - PMC - PubMed
    1. Andreini C, Putignano V, Rosato A, Banci L. The human iron-proteome. Metallomics 2018;10(9):1223–31. doi:10.1039/c8mt00146d - DOI - PubMed
    1. Rouault TA. Mammalian iron-sulphur proteins: Novel insights into biogenesis and function. Nat Rev Mol Cell Biol 2015;16(1):45–55. doi:10.1038/nrm3909 - DOI - PubMed
    1. Kim HJ, Khalimonchuk O, Smith PM, Winge DR. Structure, function, and assembly of heme centers in mitochondrial respiratory complexes. Biochim Biophys Acta - Mol Cell Res 2012;1823(9):1604–16. doi:10.1016/j.bbamcr.2012.04.008 - DOI - PMC - PubMed
    1. Poulos TL. Heme enzyme structure and function. Chem Rev 2014;114(7):3919–62. doi:10.1021/cr400415k - DOI - PMC - PubMed

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